Houston, Texas 77030


Purpose:

The goal of Phase 1B of this clinical research study is to find a dose of Taladegib that can be given safely with the chemotherapy drugs carboplatin and paclitaxel and radiotherapy to patients with esophageal or gastroesophageal junction cancer. The goal of Phase 2 of this clinical research study is to learn if Taladegib given with chemoradiation can help to control the disease. The safety of this treatment combination will continue to be studied.


Study summary:

Study Groups: If you are found to be eligible to take part in this study, you will be assigned to a study group (Phase 1B or Phase 2) based on when you join this study. If you are in Phase 1B, the dose of Taladegib that you will receive is based on when you join the study. Up to 2 doses of Taladegib will be tested. Up to 6 participants will be enrolled at each dose level. Your study doctor will tell you what dose of study drug you will receive and how this compares to the dose other participants have received. If you are in Phase 2, you will receive the dose of Taladegib found to be tolerable in Phase 1B. Study Treatment: Phase IB: You will start Taladegib on the same day you begin chemoradiation. You will take Taladegib every day until you complete chemoradiation. Phase 2: If you are one of the first 27 participants enrolled in Phase 2, you will take Taladegib for 7 days before you begin chemoradiation. If you join the study after 27 participants have been enrolled, you will start Taladegib on the same day you begin chemoradiation. You will continue to take Taladegib every day until you complete chemoradiation. Phase 1B and Phase 2: You will take Taladegib 1 time a day by mouth in the morning. You may take Taladegib with or without food. Each tablet should be taken at about the same time each morning. If you forget to take a dose, you should skip that dose and take the next dose on schedule. You will not need to make up missed doses. You will be asked to record all doses and the time taken in a drug diary. You will be asked to bring the diary, along with unused tablets and pill bottles, to each study visit. You will receive radiation every weekday for 5 ½ weeks. Once a week during this time, you also will receive paclitaxel by vein over about 3 hours followed by carboplatin by vein over about 2 hours. You will receive the chemotherapy drugs in this study either by vein (through a needle and tube that is placed in your vein for a short time) or through a central venous catheter (CVC), if you already have one placed. A CVC is a sterile flexible tube that was placed into a your large vein while you were under local anesthesia. Study Visits: Every week during treatment with Taladegib and chemoradiation, blood (about 3 tablespoons) will be drawn for routine tests. If you can become pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test every 2-4 weeks during treatment. If you are enrolled in Phase 1B, every week you will have a physical exam. If you are enrolled in Phase 2: - Every 2 weeks you will have a physical exam. - You will have an endoscopy with ultrasound and biopsy performed about 8 days after your first dose of Taladegib for biomarker testing. Tests Before Surgery: Five (5) to 6 weeks after completion of Taladegib and chemoradiation, you will have testing to check the status of the disease and to help your doctor decide if you should have surgery: - You will have a physical exam. - You will have a CT or PET/CT scan. - Blood (about 3 tablespoons) will be drawn for routine tests. - You will have an endoscopy with ultrasound and biopsy. If the tests show you can have surgery, you will sign a standard consent form for the surgery. Some of the tissue collected during your surgery will be used for biomarker testing. If you are not able to have surgery, you will be taken off study. Length of Treatment: Your treatment on this study will be over once you finish Taladegib, chemoradiation, and surgery, or Taladegib and chemoradiation alone if you do not have surgery. You will no longer be able to take the treatment if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over after the follow-up visits. Follow-Up after Surgery: About 3 months after surgery: - You will have a physical exam. - You will have an endoscopy, ultrasound (if needed), and biopsy performed. - Blood (about 3 tablespoons) will be drawn for routine tests. - If your doctor thinks it is needed, you will have a PET/CT or CT scan. After Month 3, every 3-6 months for the first year after surgery: - You will have a physical exam. - Blood (about 3 tablespoons) will be drawn for routine tests. - You will have a PET/CT or CT scan to check the status of the disease. Every 6 months during Years 2 and 3: - You will have a physical exam. - Blood (about 3 tablespoons) will be drawn for routine tests. - You will have a PET/CT or CT scan to check the status of the disease. - If your doctor thinks it is needed, you will have an endoscopy with ultrasound and biopsy. At Years 4 and 5: - You will have a physical exam. - Blood (about 3 tablespoons) will be drawn for routine tests. - You will have a PET/CT or CT scan to check the status of the disease. Once study treatment is completed, the study staff will continue to follow how you are doing for up to 5 years. If you stop coming to MD Anderson, you will be contacted by phone every 3 months. The phone call should last about 5 minutes. This is an investigational study. Taladegib is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work. The combination of carboplatin, paclitaxel, and radiation is a standard treatment for cancer of the esophagus and gastroesophageal junction. Up to 66 participants will be enrolled in this study. All will be enrolled at MD Anderson.


Criteria:

Inclusion Criteria: 1. Histologically or cytologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction (EAC). 2. Male or female patients whose age is greater than or equal to 18 years (Because nonclinical studies suggest that TALADEGIB may adversely affect the development and maintenance of teeth, bones, and growth plates in a pediatric population, children are excluded from this study. In addition, EAC is extremely rare in children). 3. Localized EAC and its baseline clinical stage determined as: T2-T3N0 or T1-3N+. Imaging studies suspicious for metastases must be followed with a negative biopsy before a patient can enter the study. 4. Patients with malignant celiac nodes are eligible if the primary lesion is in the mid-thoracic or distal thoracic esophagus or it is involving the gastroesophageal junction. 5. Tumor must have labeling index of greater than or equal to 5% of the nuclear Gli-1 (integral biomarker performed in the MD Anderson Cancer Center CLIA laboratory) for patient to be eligible in this trial (if enough archival tissue is not available to determine labeling index, patient must agree to a biopsy to be eligible for the study). 6. Tumor may not extend greater than 4 cm below the gastroesophageal junction. 7. ECOG performance status 0 or 1. 8. All patients must be willing to provide research tumor tissue for biomarker studies at baseline (from archival tumor tissue or through endoscopy if sufficient archival tissue is not available). All patients must also allow biomarker studies on the tissue obtained through surgery to remove the primary cancer. 9. Phase II only: Patients volunteering for the Phase II part of the protocol must be willing to undergo a research endoscopy for tissue collection on day 8 (+/- 2 days) from the beginning of therapy. 10. Absolute neutrophil count greater than or equal to 1500/mm^3; Platelets greater than or equal to 100,000/mm^3; Hemoglobin greater than or equal to 8 g/dL; Serum creatinine less than or equal to 2 x Upper Limit of Normal (ULN); ALT and AST less than or equal to 2.5 x ULN; Serum bilirubin less than or equal to 1.5 x ULN. 11. Patient must be able to comprehend the approved consent document and have the willingness to sign it. The patient prior to enrollment and the administration of any protocol-specific therapy must sign the consent document. 12. Willingness and ability to comply with study procedures and follow-up examinations. 13. Must be considered medically fit for operation as determined by multidisciplinary evaluation. 14. Effects of TALADEGIB on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because Hh signal pathway inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, males and females with reproductive potential must agree to use two forms of medically approved contraceptive precautions and for at least 6 months following the last dose of biochemoradiation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 15. (# 15 continued) Women of childbearing potential are defined as follows: Having regular menstrual cycles; Has amenorrhea, irregular menstrual cycles or using a contraceptive method that precludes withdrawal bleeding; Have had a tubal ligation. Women are considered not to be of childbearing potential for the following reasons: Had hysterectomy and/or bilateral oophorectomy; Post-menopausal defined by amenorrhea for at least 1 year in a woman >45 years old. 16. Females with childbearing potential must have a negative serum pregnancy test within 14 days prior to treatment start. Exclusion Criteria: 1. Baseline clinical stage of T1N0 or inoperable T4 (unequivocal organ involvement) are to be excluded. 2. Unequivocal metastatic tumor at baseline. 3. Tracheo-esophageal (TE) fistula or direct invasion into the tracheo-bronchial mucosa. A bronchoscopy (biopsy and cytology should be performed) is required to exclude TE fistula or tracheo-bronchial involvement in patients with a tumor located at <26 cm from the incisors. 4. Cervical esophageal cancer will not be entered in this study. 5. Any prior chemotherapy, surgery, or radiotherapy for EAC. 6. Prior mediastinal irradiation (for any reason). 7. Clinically significant ulcerative colitis, inflammatory bowel disease, or partial or complete small bowel obstruction are to be excluded. 8. Malabsorption syndrome or other condition that would interfere with intestinal absorption are excluded. 9. Pregnant or nursing females are to be excluded. Pregnant women are excluded from this study because TALADEGIB is a Hh pathway-inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TALADEGIB, breastfeeding should be discontinued if the mother is treated with TALADEGIB. These potential risks may also apply to other agents used in this study. 10. Presence of other significant cancer(s) or history of other significant cancer(s) within the last 3 years (patients who have been cancer-free for 3 years, or have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma of the cervix are eligible). 11. Known active viral or other chronic types hepatitides (Hepatitis B, C) or cirrhosis. 12. Uncontrolled concurrent illness including, but not limited to: serious uncontrolled infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia that interfere with blood pressure, uncontrolled diabetes, or psychiatric illness/social situations that would limit compliance with the study requirements. 13. Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation. 14. Patients who are receiving concurrent non-protocol anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or tumor embolization) are to be excluded. 15. Patients may not be receiving any other investigational agents. 16. Patients with known hypersensitivity to taxanes or platinums are to be excluded. 17. Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible. Patients on strong CYP3A inhibitors will also be excluded. 18. Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with TALADEGIB. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. 19. Any other conditions or circumstances that would, in the opinion of the Investigator, make the patient unsuitable for participation in the study.


NCT ID:

NCT02530437


Primary Contact:

Principal Investigator
Jaffer Ajani, MD
M.D. Anderson Cancer Center

Jaffer Ajani, MD
Phone: 713-792-2828
Email: CR_Study_Registration@mdanderson.org


Backup Contact:

N/A


Location Contact:

Houston, Texas 77030
United States

Clinical Research Operations
Email: CR_Study_Registration@mdanderson.org

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 21, 2017

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